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Journal of Virology, February 2008, p. 1591-1599, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01792-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

In Vivo Efficacy of Human Immunodeficiency Virus Neutralizing Antibodies: Estimates for Protective Titers{triangledown}

Alexandra Trkola,1* Herbert Kuster,1 Peter Rusert,1 Viktor von Wyl,1 Christine Leemann,1 Rainer Weber,1 Gabriela Stiegler,2 Hermann Katinger,2 Beda Joos,1 and Huldrych F. Günthard1

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland,1 Polymun Scientific, Vienna, Austria2

Received 15 August 2007/ Accepted 6 November 2007

The definition of plasma neutralizing antibody titers capable of controlling human immunodeficiency virus (HIV) infection in vivo is considered a critical step in vaccine development. Here we provide estimates for effective neutralization titers by assessing samples from a recent passive immunization trial with the neutralizing monoclonal antibodies (MAbs) 2G12, 2F5, and 4E10 using an analytic strategy that dissects the contributions of these MAbs to the total neutralization activity in patient plasma. Assessment of neutralization activities for six responding patients with partial or complete control of viremia during the MAb treatment and for the eight nonresponding patients revealed a significant difference between these groups: Among responders, MAb-mediated activity exceeded the autologous neutralization response by 1 to 2 log units (median difference, 43.3-fold), while in the nonresponder group, the autologous activity prevailed (median difference, 0.63-fold). In order to reach a 50% proportion of the responders in our study cohort, MAb neutralizing titers higher than 1:200 were required based on this analysis. The disease stage appears to have a significant impact on the quantities needed, since titers above 1:1,000 were needed to reach the same effect in chronic infection. Although our analysis is based on very small sample numbers and thus cannot be conclusive, our data provide a first estimate on how in vitro-measured neutralizing antibody activity can relate to in vivo efficacy in controlling HIV infection and may therefore provide valuable information for vaccine development. Interestingly, lower neutralizing antibody levels showed an effect in acute compared to chronic infection, suggesting that in early disease stages, therapeutic vaccination may show promise. Equally, this raises hopes that a preventive vaccine could become effective at comparatively lower neutralizing antibody titers.

* Corresponding author. Mailing address: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Rämistrasse 100, 8091 Zürich, Switzerland. Phone: 41 44 255 5976. Fax: 41 44 255 3291. E-mail: alexandra.trkola{at}usz.ch

{triangledown} Published ahead of print on 21 November 2007.

Journal of Virology, February 2008, p. 1591-1599, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01792-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Huarte, N., Lorizate, M., Maeso, R., Kunert, R., Arranz, R., Valpuesta, J. M., Nieva, J. L. (2008). The Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 4E10 Monoclonal Antibody Is Better Adapted to Membrane-Bound Epitope Recognition and Blocking than 2F5. J. Virol. 82: 8986-8996 [Abstract] [Full Text]  


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